I thought it might be worthwhile to have a discussion comparing and contrasting the symptoms of an acute infection (a week or two of flu, cold, staph, etc.) and ME/CFS. Viral persistence is often mentioned in discussions of mechanism theories. I personally think there's a good chance ME/CFS is literally a "long" infection. Maybe something is wrong with the immune system that allowed it to become "long", but just in terms of symptoms, simple infection might be able to mostly explain those. This paper did something like this comparing and contrasting: A narrative review on the similarities and dissimilarities between [ME/CFS] and sickness behavior, 2013, Morris et al Here's their table comparing the symptoms of each: Link There are a lot of similarities in symptoms: I think one of the biggest questions to drill down on is, does PEM occur in acute illness in otherwise healthy people? If it does, I think that'd be strong evidence that the two conditions are related (and evidence of what PEM is). In that case, the difference between the two would be some unknown factor that allowed the pathogen to hide away somewhere. If acute illness doesn't include PEM, that doesn't necessarily mean ME/CFS is not pathogen persistence. In that case, maybe the reason an infection becomes a "long" infection is precisely because of PEM: someone with ME/CFS's immune system gets all wonky after exertion, which allows the pathogen to spread and take root somewhere, and this doesn't occur in healthy people because exertion doesn't mess with their immune system. The paper says: I mean, most everyone has been sick, and we don't really think of PEM as being a part of it. But I think there are potential explanations for that. First, the short duration of acute infections. It's only a week or two, where someone's energy levels and other symptoms are already rapidly changing over only a few days. If someone went for a run while sick, then got even worse two days later, I can see how they might think their illness just got a bit worse, as illnesses sometimes do, and it had no connection to the running. They don't have the advantage (ha) that people with ME/CFS do, where they experience PEM over and over and over, and can start to detect a pattern of exertion causing it. From what I recall, it took me quite a long time to realize fatigue randomly getting much worse was tied to something like a long walk two days before. Because why would I ever think that when I've been told my whole life that exercise can only be healthy. Second, maybe they do make the connection that exercise caused them to get worse after a day or two, but they don't think of it as "PEM". Maybe they think of it as "I went for a run, and that weakened my immune system, so the infection got worse." The symptoms might be similar, but doesn't seem obviously to be the same as PEM, because in acute infection the "effect" is "worse infection", with its expected increase in fatigue and other symptoms, while in ME/CFS, the "effect" is "worse fatigue and other symptoms". The lack of infection in ME/CFS to explain things might get in the way of seeing the similarities in symptoms.
Data that would be useful for this would be how bed rest affects the duration/severity of a sickness. That's the commonly prescribed advice from our doctors and parents. "Rest so that the body can heal." If this advice is based on a real effect, I think that's basically evidence of PEM: if you get up and exercise, your sickness will get worse. I found an observational study from 1936 (!) that looked at the effect of delaying bed rest on acute illness: The common cold and the effect of rest in bed on its course, 1936, LeBlanc et al They compared nurses hospitalized for "common cold" that reported that they started bed rest within 30 hours after the start of their infection symptoms, with those that waited longer. Being an observational study, there are of course confounders that make it difficult to infer causality, some of which they go into: I don't see how the limitations they list could explain illness being so much worse in the delayed group. It seems they would explain the opposite. But I'm sure there might be reasons people who waited longer to rest got sicker. One possibility is maybe people who are unhealthy and prone to severe complications are unhealthy because they are worse off socioeconomically, and thus would work longer to not miss out on the money. These are all nurses, so I assume their incomes are similar, but maybe some have wealthier family which allows them better healthcare and diet, and less need to work through a sickness. Nevertheless, the outcomes at least support the possibility that not resting during a cold leads to worse illness. Non-delayed group entered the hospital and commenced bed rest an average of 18.8 hours after onset. Delayed group entered hospital 138 hours after onset. They measured days of fever, days in hospital, days off duty, total length of illness, loss of weight, and number of nurses with complications. All were worse in delayed group, although fever and weight loss were not significant. Strikingly, the delayed group had over five times the prevalence of complications. I'll see if there are any more bed rest studies. I assume an RCT wouldn't be approved as ethical, but who knows.
My first PEM episode was hard to distinguish from the initial phase of a mild infection, where the fever hasn't yet started but you can feel that you're sick. In September I probably had covid and it took a few days to realize it was an infection and not just ME/CFS. when the infection / immune response peaks and fever appears, it's clearly distinguishable from ME/CFS, but before that it can pass for ME/CFS.
Similar for me, I can only be sure PEM isn't a virus when it stops at sore throat, swollen glands, and a slightly runny nose. It never causes sneezing, coughing, sinus pain or earache, and while PEM sore throat's annoying, it isn't as painful as some colds. But while it seems plausible that some of the 'bleuurgh' in PEM is caused by the same immune factors as the response to a respiratory virus, I'd argue it's important to regard it as different for now. If researchers make assumptions, they could completely miss the most important clue.
The fever and the symptom profile and intensity. It just feels different. I wonder if the "feels like the beginning of an infection" is a clue that the innate immune system is a key player in ME/CFS.
Surprisingly, I found an RCT of bed rest for tuberculosis. Also an old paper. Bed rest in the treatment of pulmonary tuberculosis, 1956, Tyrrell et al They admitted every other patient who presented with TB to a hospital for 3 to 6 months bed rest, and instructed the rest to continue normal exercise. The conclusion was basically they found no differences in outcomes.
I experienced delayed muscle weakness/fatigue in my legs from Covid infection after going out for my regular power walk after I felt recovered. It did not affect my cognitive energy. It was not the same experience as ME/CFS delayed full body toxic PEM.
I should also mention that in early 2000 when HHV6 and EBV was reactivated I had to rest for 2.5 months. I went out for a short run after I felt recovered and the next day the delayed PEM completely changed my baseline for good. This was when OI set in and I've had it ever since.
Another two that found no benefit from bed rest in tuberculosis: Is cavity closure in pulmonary tuberculosis influenced by bed-rest?, 1960, Wynn-Williams et al I can't access this one, but the article below it describes the results: Late Results of Modified Bed Rest in Active Uncomplicated Minimal Pulmonary Tuberculosis, 1953, Mitchell Bed rest in tuberculosis An RCT of bed rest in infectious mononucleosis also found no benefit: INFECTIOUS MONONUCLEOSIS. 2. RELATION OF BED REST AND ACTIVITY TO PROGNOSI, 1964, Dalrymple No benefit found in a review focused on rheumatic fever: Role of bed rest in treatment of rheumatic fever; review of literature and survey of current opinions, 1957, Duman et al ---- I think there is a possibility that bed rest has no benefit if the patient doesn't desire to rest. Maybe only if someone is very tired from an infection and is forced to exercise/work will they have a worse outcome. For example, the mono study above said the non-bed rest group did activity "as desired", so maybe their body didn't require rest to heal.
Yes, I was wondering why I'm seeing so many papers talking about bed rest in TB, but almost none in other infections.
